tbuckley/cabot-search huggingface dataset:
Seed amplification assay of nasal swab extracts for accurate and non-invasive molecular diagnosis of neurodegenerative diseases
Authors: Suying Duan, Jing Yang, Zheqing Cui, Jiaqi Li, Honglin Zheng, Taiqi Zhao, Yanpeng Yuan, Yutao Liu, Lu Zhao, Yangyang Wang, Haiyang Luo, Yuming Xu
Journal: Translational Neurodegeneration (2023)

Abstract Nasal swabs are non-invasive testing methods for detecting diseases by collecting samples from the nasal cavity or nasopharynx. Dysosmia is regarded as an early sign of coronavirus disease 2019 (COVID-19), and nasal swabs are the gold standard for the detection. By nasal swabs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids can be cyclically amplified and detected using real-time reverse transcriptase-polymerase chain reaction after sampling. Similarly, olfactory dysfunction precedes the onset of typical clinical manifestations by several years in prion diseases and other neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. In neurodegenerative diseases, nasal swab tests are currently being explored using seed amplification assay (SAA) of pathogenic misfolded proteins, such as prion, α-synuclein, and tau. These misfolded proteins can serve as templates for the conformational change of other copies from the native form into the same misfolded form in a prion-like manner. SAA for misfolded prion-like proteins from nasal swab extracts has been developed, conceptually analogous to PCR, showing high sensitivity and specificity for molecular diagnosis of degenerative diseases even in the prodromal stage. Cyclic amplification assay of nasal swab extracts is an attractive and feasible method for accurate and non-invasive detection of trace amount of pathogenic substances for screening and diagnosis of neurodegenerative disease. Graphical Abstract
Environmental surveillance of antimicrobial resistance (AMR), perspectives from a national environmental regulator in 2023
Authors: Alwyn Hart, Jonathan Warren, Helen Wilkinson, Wiebke Schmidt
Journal: Eurosurveillance (2023)

The development, and in some cases increasing prevalence, of resistance to antimicrobials used in clinical and veterinary settings has long been recognised. In recent years, the concept of 'One Health' has added recognition of the role that the environment plays in health protection along with the need for protection of the health of the environment itself. Organisations including the World Health Organization, United Nations Environment Programme, and national governments have identified a need for surveillance of antimicrobial resistance in the environment to sit alongside the surveillance carried out in clinical, veterinary and food sectors. However, having recognised the need for environmental surveillance there are multiple challenges in deciding what this should entail. For example, what pathogens or genes to monitor, who or what we wish to protect and what measures we wish to enable to decrease infection risks. That might include sampling near a source of resistant organisms entering the environment or conversely sampling where the exposure actually occurs. Choices need to be made at both policy and technical levels based on the detailed purposes of surveillance. This paper discusses these issues from the perspective of a national environmental regulator.
Undeclared pre-exposure or post-exposure prophylaxis (PrEP/PEP) use among syphilis-positive blood donors, England, 2020 to 2021
Authors: Victoria Maddox, Claire Reynolds, Alieu Amara, Laura Else, Susan R Brailsford, Saye Khoo, Heli Harvala
Journal: Eurosurveillance (2023)

An individualised blood donor selection policy was implemented in the United Kingdom from summer 2021. We have investigated the impact of this policy by comparing the extent of undeclared use of HIV pre-exposure or post-exposure prophylaxis (PrEP/PEP) before and after this change. The rate of PrEP usage in syphilis-positive male blood donors has not changed since individualised donor assessment was implemented but provides continuing evidence of undisclosed PrEP use which may be associated with current or past higher-risk sexual behaviours.
GPR120 promotes neutrophil control of intestinal bacterial infection
Authors: Zheng Zhou, Wenjing Yang, Tianming Yu, Yu Yu, Xiaojing Zhao, Yanbo Yu, Chuncai Gu, Anthony J Bilotta, Suxia Yao, Qihong Zhao, George Golovko, Mingsong Li, Yingzi Cong
Journal: Gut Microbes (2023)

G-protein coupled receptor 120 (GPR 120) has been implicated in anti-inflammatory functions. However, how GPR120 regulates the neutrophil function remains unknown. This study investigated the role of GPR120 in the regulation of neutrophil function against enteric bacteria. 16S rRNA sequencing was used for measuring the gut microbiota of wild-type (WT) mice and Gpr120−/− mice. Citrobacter rodentium infection and dextran sulfate sodium (DSS)-induced colitis models were performed in WT and Gpr120−/− mice. Mouse peritoneal-derived primary neutrophils were used to determine the neutrophil functions. Gpr120−/− mice showed altered microbiota composition. Gpr120−/− mice exhibited less capacity to clear intestinal Citrobacter rodentium and more severe intestinal inflammation upon infection or DSS insults. Depletion of neutrophils decreased the intestinal clearance of Citrobacter rodentium. GPR120 agonist, CpdA, enhanced WT neutrophil production of reactive oxygen species (ROS) and extracellular traps (NETs), and GPR120-deficient neutrophils demonstrated a lower level of ROS and NETs. CpdA-treated neutrophils showed an enhanced capacity to inhibit the growth of Citrobacter rodentium, which was abrogated by the inhibition of either NETs or ROS. CpdA promoted neutrophil inhibition of the growth of commensal bacteria Escherichia coli O9:H4 and pathobiont Escherichia coli O83:H1 isolated from a Crohn's disease patient. Mechanically, mTOR activation and glycolysis mediated GPR120 induction of ROS and NETs in neutrophils. Additionally, CpdA promoted the neutrophil production of IL-17 and IL-22, and treatment with a conditioned medium of GPR120-activated neutrophils increased intestinal epithelial cell barrier functions. Our study demonstrated the critical role of GPR120 in neutrophils in protection against enteric bacterial invasion.
Legionnaires’ disease in the EU/EEA*: increasing trend from 2017 to 2019
Authors: Jonas Samuelsson, Lara Payne Hallström, Gaetano Marrone, Joana Gomes Dias
Journal: Eurosurveillance (2023)

BackgroundThe burden of Legionnaires' disease (LD) in the European Union/European Economic Area (EU/EEA) has increased during the last decade, with notification rates increasing from 1.2 to 1.4/100,000 population in 2012-16, to 1.8-2.2 within 2017-19.AimTo measure weekly excess cases during 2017-19 based on previous trends and determine whether a significant change in trend occurred, and to examine any differences in age, sex or level of imported infections.MethodsWe collated 2012-19 annual surveillance data from The European Surveillance System (TESSy) reported by EU/EEA countries. A retrospective prediction by a dynamic regression model was created from 2012-16 data to assess excess cases in 2017-19. Interrupted time series (ITS) analysis was performed to determine if a significant change in trend occurred in 2017-19 compared with the previous 5 years.ResultsWe found a 33.9% increase in cases in 2017-19 compared with the number predicted. The ITS also found a significant trend increase in 2017-19 compared with 2012-16. A significant trend increase was observed from 2017 most strongly among older age groups (> 60 years) and non-imported cases.ConclusionOur study showed a significant increasing trend in LD cases in the EU/EEA during 2017-19 compared with the previous 5 years. The distribution of cases per week suggests an overall amplification of the seasonal trends. These findings underscore that LD continues to be an infectious disease of public health concern in the EU/EEA, warranting further research into determinants of the increase.
Effects of Time-Restricted Eating on Nonalcoholic Fatty Liver Disease
Authors: Xueyun Wei, Bingquan Lin, Yan Huang, Shunyu Yang, Chensihan Huang, Linna Shi, Deying Liu, Peizhen Zhang, Jiayang Lin, Bingyan Xu, Dan Guo, Changwei Li, Hua He, Shiqun Liu, Yaoming Xue, Yikai Xu, Huijie Zhang
Journal: JAMA Network Open (2023)

Importance The efficacy and safety of time-restricted eating (TRE) on nonalcoholic fatty liver disease (NAFLD) remain uncertain. Objective To compare the effects of TRE vs daily calorie restriction (DCR) on intrahepatic triglyceride (IHTG) content and metabolic risk factors among patients with obesity and NAFLD. Design, Setting, and Participants This 12-month randomized clinical trial including participants with obesity and NAFLD was conducted at the Nanfang Hospital in Guangzhou, China, between April 9, 2019, and August 28, 2021. Interventions Participants with obesity and NAFLD were randomly assigned to TRE (eating only between 8:00 am and 4:00 pm ) or DCR (habitual meal timing). All participants were instructed to maintain a diet of 1500 to 1800 kcal/d for men and 1200 to 1500 kcal/d for women for 12 months. Main Outcomes and Measures The primary outcome was change in IHTG content measured by magnetic resonance imaging; secondary outcomes were changes in body weight, waist circumference, body fat, and metabolic risk factors. Intention-to-treat analysis was used. Results A total of 88 eligible patients with obesity and NAFLD (mean [SD] age, 32.0 [9.5] years; 49 men [56%]; and mean [SD] body mass index, 32.2 [3.3]) were randomly assigned to the TRE (n = 45) or DCR (n = 43) group. The IHTG content was reduced by 8.3% (95% CI, −10.0% to −6.6%) in the TRE group and 8.1% (95% CI, −9.8% to −6.4%) in the DCR group at the 6-month assessment. The IHTG content was reduced by 6.9% (95% CI, −8.8% to −5.1%) in the TRE group and 7.9% (95% CI, −9.7% to −6.2%) in the DCR group at the 12-month assessment. Changes in IHTG content were comparable between the 2 groups at 6 months (percentage point difference: −0.2; 95% CI, −2.7 to 2.2; P = .86) and 12 months (percentage point difference: 1.0; 95% CI, −1.6 to 3.5; P = .45). In addition, liver stiffness, body weight, and metabolic risk factors were significantly and comparably reduced in both groups. Conclusions and Relevance Among adults with obesity and NAFLD, TRE did not produce additional benefits for reducing IHTG content, body fat, and metabolic risk factors compared with DCR. These findings support the importance of caloric intake restriction when adhering to a regimen of TRE for the management of NAFLD. Trial Registration ClinicalTrials.gov Identifiers: NCT03786523 and NCT04988230
Erratum: Current Breast Milk PFAS Levels in the United States and Canada: After All This Time, Why Don’t We Know More?
Authors: Judy S. LaKind, Marc-André Verner, Rachel D. Rogers, Helen Goeden, Daniel Q. Naiman, Satori A. Marchitti, Geniece M. Lehmann, Erin P. Hines, Suzanne E. Fenton
Journal: Environmental Health Perspectives (2023)
Development of a Machine Learning Model to Estimate US Firearm Homicides in Near Real Time
Authors: Elizabeth A. Swedo, Alen Alic, Royal K. Law, Steven A. Sumner, May S. Chen, Marissa L. Zwald, Miriam E. Van Dyke, Daniel A. Bowen, James A. Mercy
Journal: JAMA Network Open (2023)

Firearm homicides are a major public health concern; lack of timely mortality data presents considerable challenges to effective response. Near real-time data sources offer potential for more timely estimation of firearm homicides.To estimate near real-time burden of weekly and annual firearm homicides in the US.In this prognostic study, anonymous, longitudinal time series data were obtained from multiple data sources, including Google and YouTube search trends related to firearms (2014-2019), emergency department visits for firearm injuries (National Syndromic Surveillance Program, 2014-2019), emergency medical service activations for firearm-related injuries (biospatial, 2014-2019), and National Domestic Violence Hotline contacts flagged with the keyword firearm (2016-2019). Data analysis was performed from September 2021 to September 2022.Weekly estimates of US firearm homicides were calculated using a 2-phase pipeline, first fitting optimal machine learning models for each data stream and then combining the best individual models into a stacked ensemble model. Model accuracy was assessed by comparing predictions of firearm homicides in 2019 to actual firearm homicides identified by National Vital Statistics System death certificates. Results were also compared with a SARIMA (seasonal autoregressive integrated moving average) model, a common method to forecast injury mortality.Both individual and ensemble models yielded highly accurate estimates of firearm homicides. Individual models' mean error for weekly estimates of firearm homicides (root mean square error) varied from 24.95 for emergency department visits to 31.29 for SARIMA forecasting. Ensemble models combining data sources had lower weekly mean error and higher annual accuracy than individual data sources: the all-source ensemble model had a weekly root mean square error of 24.46 deaths and full-year accuracy of 99.74%, predicting the total number of firearm homicides in 2019 within 38 deaths for the entire year (compared with 95.48% accuracy and 652 deaths for the SARIMA model). The model decreased the time lag of reporting weekly firearm homicides from 7 to 8 months to approximately 6 weeks.In this prognostic study of diverse secondary data on machine learning, ensemble modeling produced accurate near real-time estimates of weekly and annual firearm homicides and substantially decreased data source time lags. Ensemble model forecasts can accelerate public health practitioners' and policy makers' ability to respond to unanticipated shifts in firearm homicides.
Tap water as the source of a Legionnaires’ disease outbreak spread to several residential buildings and one hospital, Finland, 2020 to 2021
Authors: Silja Mentula, Sohvi Kääriäinen, Sari Jaakola, Marjo Niittynen, Piia Airaksinen, Irma Koivula, Markku Lehtola, Ella Mauranen, Isto Mononen, Raija Savolainen, Susanna Haatainen, Outi Lyytikäinen
Journal: Eurosurveillance (2023)

In Finland, all microbiology laboratories notify Legionella findings and physicians notify Legionnaires' disease (LD) cases to the National Infectious Disease Register. All cases are interviewed, and water samples obtained from potential places of exposure. Legionella isolates from humans and water are compared by whole genome sequencing (WGS). In March 2021, Legionella pneumophila serogroup 1 (Lp 1) pneumonia cases increased in one Finnish city (120,000 inhabitants) where single LD cases are detected annually. We identified 12 LD cases, nine living in different residential buildings and three nosocomial, linked by identical human and/or water isolates. Three of these cases were from January 2020, October 2020 and February 2021 and identified retrospectively. Eleven were diagnosed by urinary antigen test, 10 by PCR and five by culture; age ranged between 52 and 85 years, and 10 had underlying diseases. Nine of 12 homes of LD cases and 15 of 26 water samples from the hospital were positive for Lp 1, with concentrations up to 640,000 cfu/L. Water samples from regional storage tanks were negative. Positivity in homes and the hospital suggested inadequate maintenance measures. Enhanced surveillance combined with WGS was crucial in detecting this unusual LD outbreak related to domestic and hospital water systems.
Letter to the Editor: Association between birth weight, preterm birth, and nonalcoholic fatty liver disease in a community-based cohort
Authors: Rabia Irfan, Satesh Kumar
Journal: Hepatology (2023)

To the editor, We have read the study "Association between birth weight, preterm birth, and NAFLD in a community-based cohort" by Amadou et al.1 This article confirms the association between birth weight and NAFLD. We appreciate the various factors that were considered. Yet, we would like to add a few points that will strengthen the study's validity. Ultrasonography is the first-line screening marker for diagnosing hepatic steatosis; however, a liver biopsy is a gold standard.2 Second, the author should have addressed the significant correlation between birth weight and NAFLD severity. According to a study conducted with biopsy-confirmed NAFLD, children born with a high birth weight have an increased risk of developing liver steatosis, while those born with a low birth weight have an increased risk of developing liver fibrosis.3 Although the author has mentioned essential risk factors that can lead to NAFLD, we hypothesize a vital relationship between genetic and epigenetic factors that should be considered when predicting fatty liver in adults. PNPLA3, also known as patatin-like phospholipase-3, is a lipase found in adipocytes and hepatocytes. Triglyceride breakdown is inhibited by the PNPLA3 l148 mutation, resulting in lipid retention in hepatocyte lipid droplets. The G allele of PNPLA3's rs738409 was strongly associated with increased NAFLD risk. Children born small for their gestational age experience rapid weight gain early in life, resulting in insulin resistance and metabolic complications that may lead to NAFLD. An abnormal lipid profile, obesity, and diabetes characterize the metabolic syndrome. On the other hand, the G allele was associated with a favorable metabolic profile. Still, individuals carrying this allele may have enough steatosis that can lead to fibrosis and cirrhosis. Therefore, the genetic analysis should be conducted so that the primary cause can be targeted selectively, and interventions should be designed accordingly.4
Mechanism of epithelial‐mesenchymal transition in cancer and its regulation by natural compounds
Authors: Hui Li Ang, Chakrabhavi Dhananjaya Mohan, Muthu K. Shanmugam, Hin Chong Leong, Pooyan Makvandi, Kanchugarakoppal S. Rangappa, Anupam Bishayee, Alan Prem Kumar, Gautam Sethi
Journal: Medicinal Research Reviews (2023)

Abstract Epithelial‐mesenchymal transition (EMT) is a complex process with a primordial role in cellular transformation whereby an epithelial cell transforms and acquires a mesenchymal phenotype. This transformation plays a pivotal role in tumor progression and self‐renewal, and exacerbates resistance to apoptosis and chemotherapy. EMT can be initiated and promoted by deregulated oncogenic signaling pathways, hypoxia, and cells in the tumor microenvironment, resulting in a loss‐of‐epithelial cell polarity, cell–cell adhesion, and enhanced invasive/migratory properties. Numerous transcriptional regulators, such as Snail, Slug, Twist, and ZEB1/ZEB2 induce EMT through the downregulation of epithelial markers and gain‐of‐expression of the mesenchymal markers. Additionally, signaling cascades such as Wnt/β‐catenin, Notch, Sonic hedgehog, nuclear factor kappa B, receptor tyrosine kinases, PI3K/AKT/mTOR, Hippo, and transforming growth factor‐β pathways regulate EMT whereas they are often deregulated in cancers leading to aberrant EMT. Furthermore, noncoding RNAs, tumor‐derived exosomes, and epigenetic alterations are also involved in the modulation of EMT. Therefore, the regulation of EMT is a vital strategy to control the aggressive metastatic characteristics of tumor cells. Despite the vast amount of preclinical data on EMT in cancer progression, there is a lack of clinical translation at the therapeutic level. In this review, we have discussed thoroughly the role of the aforementioned transcription factors, noncoding RNAs (microRNAs, long noncoding RNA, circular RNA), signaling pathways, epigenetic modifications, and tumor‐derived exosomes in the regulation of EMT in cancers. We have also emphasized the contribution of EMT to drug resistance and possible therapeutic interventions using plant‐derived natural products, their semi‐synthetic derivatives, and nano‐formulations that are described as promising EMT blockers.
Diversified Mammalian Visual Adaptations to Bright- or Dim-Light Environments
Authors: Yulin Gai, Ran Tian, Fangnan Liu, Yuan Mu, Lei Shan, David M Irwin, Yang Liu, Shixia Xu, Guang Yang
Journal: Molecular Biology and Evolution (2023)

Abstract Photic niche shifts of mammals are associated with changing visual capabilities, primarily mediated by three visual pigments, two (SWS1 and M/LWS) of them for color vision and rhodopsin (RH1) for dim-light vision. To further elucidate molecular mechanisms of mammalian visual adaptations to different light environments, a systematic study incorporating evolutionary analyses across diverse groups and in vitro assays have been carried out. Here, we collected gene sequences for the three opsins from 220 species covering all major mammalian clades. After screening for cone opsin gene losses, we estimated selective pressures on each of the three genes and compared the levels of selection experienced by species living in bright- and dim-light environments. SWS1 pigment is shown to experience accelerated evolution in species living in bright-light environments as has RH1 in aquatic cetaceans, indicating potential shifts for ecological adaptations. To further elucidate the functional mechanisms for these two pigments, we then carried out site-directed mutagenesis in representative taxa. For SWS1, violet and ultraviolet sensitivities in the pika and mouse are mainly affected by substitutions at the critical sites 86 and 93, which have strong epistatic interaction. For RH1, the phenotypic difference between the sperm whale and bovine sequences is largely contributed by a substitution at site 195, which could be critical for dim-light sensation for deep-diving species. Different evolutionary patterns for the visual pigments have been identified in mammals, which correspond to photic niches, although additional phenotypic assays are still required to fully explain the functional mechanisms.